The role of mitochondria in cytoplasmic Ca2+ cycling

It has been known for a long time that isolated mitochondria are able to accumulate large amounts of calcium ions. Before the discovery that endoplasmic reticulum (ER) was the main Ca(2+)-storing cellular organelle, mitochondria were thought to play a major role in cytoplasmic Ca(2+) homeostasis (Carafoli, 2002). After IP(3) was discovered and it was shown that IP(3) receptors were localized in ER membrane and that Ca(2+)-binding proteins such as calsequestrin could store large amounts of Ca(2+) in the ER, the role of mitochondria in the regulation of cytoplasmic Ca(2+) was questioned. However, in recent years, mostly due to the development of new methods, there has been increasing evidence that mitochondria could be an important cytoplasmic Ca(2+) sink, especially under conditions of a high cellular Ca(2+) load.